May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Age-Related, Light-Independent Retinal Degeneration in NRL/GRK1 Knockout Mice
C. M. Craft; B. M. Brown; L. Rife
Author Affiliations & Notes
  • C. M. Craft
    Keck School of Medicine of the University of Southern California, Los Angeles, California
    Mary D. Allen Laboratory for Vision Research, Doheny Eye Inst., Ophthalmology & Cell & Neurobiology,
  • B. M. Brown
    Keck School of Medicine of the University of Southern California, Los Angeles, California
    Mary D. Allen Laboratory for Vision Research, Doheny Eye Inst., Ophthalmology & Cell & Neurobiology,
  • L. Rife
    Keck School of Medicine of the University of Southern California, Los Angeles, California
    Ophthalmology,
  • Footnotes
    Commercial Relationships C.M. Craft, None; B.M. Brown, None; L. Rife, None.
  • Footnotes
    Support Mary D. Allen Endowed Chair, DEI (CMC), Mary D. Allen Foundation (CMC), NIH Grant EY015851 (CMC), EY03040 (DEI), RPB (DEI)
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 3001. doi:
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      C. M. Craft, B. M. Brown, L. Rife; Age-Related, Light-Independent Retinal Degeneration in NRL/GRK1 Knockout Mice. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3001.

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Abstract

Purpose:: Retinal degeneration occurs in a pure cone retina model of dark reared NRL/G protein-coupled receptor kinase 1 (GRK1) double knockout (Nrl-/-Grk1-/-) mice compared to Nrl-/-.1 To characterize the environmental influence of light exposure and age progression on maturation and metabolism of cones in Nrl-/-Grk1-/-, further studies were initiated.

Methods:: Nrl-/- (A Swaroop & AJ Mears), Nrl-/-Arr1-/- (Arr1 -/-, J Chen), Nrl-/-Grk1-/-(Grk1-/-, CK Chen), and Nrl-/-Grk1-/-Arr1-/- mice were born and reared in either total darkness, 12hr:12hr ambient cyclic light, or 8000 lux bright constant light. Retinas were examined at 1, 3, 5, 7 and 9 months by electroretinography (ERG), immunohistochemistry (IHC), and immunoblots. At 1 month, TUNEL assays quantitated retinal apoptotic cell death.

Results:: Electrophysiological analyses measured photopic b-wave amplitude of dark-adapted ERG responses elicited by maximum light stimulus. In the 3 lighting conditions tested, with increasing age in Nrl-/-Grk1-/- mice, b-wave amplitude decreases while unchanged in Nrl-/- mice until 7 months. The Nrl-/-Grk1-/- mice cone photoreceptors slowly degenerate with age at a similar rate independent of environmental light exposure with the central inferior region of cones dying first. Immunoblot and IHC analyses reveal a parallel progressive decrease of CARR, UV- and M-opsin pigment expression in the Nrl-/-Grk1-/- mouse retina with increasing age. In contrast, cone protein expression levels remain relatively constant in the cone photoreceptors of the age-matched Nrl-/- mice. TUNEL positive cells were significantly higher in retinas of Nrl-/-Grk1-/- and Nrl-/-Grk1-/-Arr1-/- compared to retinas of Nrl-/- and Nrl-/-Arr1-/.

Conclusions:: GRK1 expression is a critical enzyme for maintaining rod and cone photoreceptor light-activated shutoff of the visual pigments. When GRK1 is defective, normal photoreceptor structure and function are compromised. In the Nrl-/-Grk1-/- mouse retina, apoptosis is light-independent and age-related. Our hypothesis is that the age-related retinal degeneration is linked to the absence of GRK1 phosphorylation or other GRK1-dependent functions. Comparative microarray and proteomic analysis will provide clues to the mechanisms that may contribute to this age-related, light-independent cone dystrophy.1 Zhu, X, et al. New Insights into Retinal Degenerative Diseases 2006;133-139

Keywords: photoreceptors • phosphorylation • age-related macular degeneration 
© 2007, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
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